The overall objective of this project is to define the development and pathogenesis of immune complex disease in guinea pig lungs. This pulmonary disease was elicited in immunized animals by exposing them to an aerosol of homologous antigen (i.e., ovalbumin). Current efforts are devoted to determining the relative contribution of antibody-forming cells in the systemic circulation and lung to the total quantity of antibodies to ovalbumin in the lung. The capacity of lung, blood, and spleen lymphocytes from immunized and challenged animals to produce these antibodies will be tested in direct and indirect plaque assays. IgGl and IgG2 antibodies can activate complement via the alternative and classical pathways, respectively. IgGl is also a potent tissue-fixing antibody. Therefore, histamine-blocking and complement-depletion studies are now in progress to elucidate the importance of the tissue-and complement-fixing activities of IgGl antibody, respectively, to the overall and thus of each of the IgG antibody subclasses in the production of lung injury initiated by antigen-antibody complexes will be further evaluated in guinea pigs deficient in the fourth component of complement. These animals can only utilize the alternative complement pathway. Finally, studies will be conducted to determine whether the pathogenic immune complexes in the lung are initially formed locally or systemically. An antiglobulin coprecipitation technique will be used to detect these complexes in lung lavage fluids and sera from actively immunized animals after intratracheal challenge with radiolabeled ovalbumin.